Individual estimates of European genetic admixture associated with lower body-mass index, plasma glucose, and prevalence of type 2 diabetes in Pima Indians

Individual genetic admixture estimates (IA) from European Americans (EAs) w ere computed in 7,996 members of the Gila River Indian Community (Arizona). Parental populations for the analysis were European Americans and full-her itage Pima Indians. A logistic regression was performed on 7,796 persons, t o assess association of IA with type 2 diabetes. The odds ratio, comparing diabetes risk in full-heritage EAs with full-heritage Pima Indians, was 0.3 29 (95% confidence interval [CI] 0.225-0.482). proportional-hazards analysi s was performed on 5,482 persons who were nondiabetic at their first examin ation and 1,215 subjects who developed diabetes during the study. The hazar d risk ratio for IA was 0.455 (95% CI 0.301-0.688). Nondiabetic persons had significantly more European IA. In nondiabetic Pimans, multivariate linear regressions of quantitative predictors of type 2 diabetes mellitus, includ ing fasting plasma glucose, 2-h post-load plasma glucose, and body-mass ind ex, showed significant inverse relations with IA when controlled for sex an d age. These results illustrate the ongoing evolution of populations by the mechanism of gene flow and its effect on disease risk in the groups with a dmixture. When the two parental populations differ in disease prevalence, h igher or lower risk is associated with admixture, depending on the origin o f the admired alleles and the relative magnitude of the disease prevalence in the parental populations. These data also illustrate the strong genetic components in type 2 diabetes and are consistent with one susceptibility lo cus common to obesity and diabetes.